17. 2011-02-23

17. 2011-02-23 - Chapter 5 Antibiotics and Antibiotic...

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Chapter 5 Antibiotics and Antibiotic Resistance in Bacteria
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5.7 Resistance: Target site modification (TSM) Cellular target site of antibiotic altered so antibiotic can’t bind to it Makes organism resistant Origin: mutation in genes encoding the protein target of the antibiotic Origins of mutations Imperfections in normal DNA replication during cell division = Errors in DNA replication because of damage to DNA by environmental agents = Breaking and joining of DNA molecules in new molecular arrangments = Spontaneous mutation Induced mutation Recombinational mutation Origins
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DNA polymerase enzyme makes unavoidable base-pairing errors in DNA replication during cell division Chemical basis of unavoidable errors? See Custom Text and Chapter 5 Learning Objectives (VISTA) Spontaneous mutation Base substitution mutations A G G T T C C G 3' T C A G T C A G DNA Template New DNA 5' Nucleotides DNA Polymerase A G C T 5' 3'
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Colonies on agar Scanning electron micrograph of cells Bar = 2 μ m Bar = 2 mm Example of target site modification leading to antibiotic- resistance that can be explained by spontaneous mutation: Mycobacterium tuberculosis : Gm +ve rod
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Rifampin an important antibiotic in TB treatment Binds to the β protein subunit of RNA polymerase disrupting transcription. Protein subunit designated RpoB RpoB is a big protein subunit = 1178 amino acids
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All bacteria have a rpoB gene encoding a RpoB protein, eg. E. coli
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Rif S wild-type M. tuberculosis and Rif R mutant M. tuberculosis exhibit the following differences that can be explained by spontaneous mutation:
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